ORIGINAL ARTICLE 

Annals of Nuclear Medicine Vol. 7, No. 4, 251-255, 1993 

Relationship between liver function and splenic blood flow (Quantitative Ineasurement of splenic blood flow with H,*=0 and a dynamic state method : 2) 

Atsushi OGURO,* Hiroki TANIGUCHI,* Hiroshi KOYAMA,* Hiroki TANAKA,* Keigo MIYATA,* Kazumi TAKEUCHI,* Tadashi INABA,** Hisamitsu NAKAHASHI** and Toshio TAKAHASHl* 

*First Department of Surgery, Kyoto Prefectural University of Medicine **Nishljin Hospital, Kyoto, Japan 

We measured splenic blood flow in 55 patients by means of quantitative splenic positron emission tomography (PET), a novel, dynamic state method with H2150 as a tracer. Twenty-four of the 55 patients suffered from liver cirrhosis (LC), 25 showed no evidence of cirrhosis (NR) and 6 patients were diagnosed as having chronic hepatitis (CH). Splenic blood flow per 100 g weight of the spleen (SBF) was significantly correlated with splenic volume (r= -0.39, p<0.005). The indocyanine green retention test at 15 min (r=-0.39, p<0.005) and the hepaplastin test (r=0.37, p<0.025) also correlated significantly with SBF. The means and 95% confidence intervals for the LC, CH, and NR groups were 1 17.5 ml/min/ 100 g (96.6-138.4), 102.5 ml/min/100 g (60.6-144.4), and 160.3 ml/min/100 g (139.8-180.8), respectively. The differences in SBF between these 3 groups were significant (p<0.01). We conclude that regional splenic blood flow is not proportionate to splenic volume, although the splenic volume does increase with the progressive chronic changes observed in hepatic diseases. 

Key words: splenic blood flow, PET, Iiver function 

INTRODUCTION 

IN A PREVIOUS STUDY, we quantified human splenic blood flow by positron emission tomography (PET) with H2150 as a tracer. The spleen often increases in size according to the severity of compromised hepatic function, and the cause of this splenomegaly is gen-erally considered to be simple congestion. However, no precise study on its pathophysiology has yet been performed. Although studies on splenic blood flow reported thus far have been semi-quantitative,1-4 such studies can now be quantified with PET. We therefore investigated the relationship between splenic blood flow (SBF) and liver function by this method. Our operating hypothesis is that liver dys-function is associated with portal hypertension and a decrease in portal venous fiow, which in turn may alter splenic blood flow and splenic volume. 

SUBJECTS AND METHODS 

Patients 
Fifty-five patients were classified into three groups referred for liver biopsy or surgical specimen, who had been informed of the significance of the study and had consented to it. The first group (LC group) included 1 8 males and 6 females, ranging in age from 34 to 74 years (mean: 56.5 years), who had liver cirrhosis (LC) : 20 of them were diagnosed as having hepatocellular carcinomas (HCC) but no liver tumors could be found in the other 4 patients. The CH group consisted of 5 males and a female ranging in age from 45 to 72 years (mean: 62.5 years) who were diagnosed as having chronic hepatitis (CH) : 4 of them had HCC as a complication and the other 2 patients had no detectable liver tumors. The final group (NR group) consisted of 16 males and 9 females with an age distribution of 32 to 77 years (mean: 56.4 years), and no history of any chronic liver disease. All but five patients in the NR group were found to have liver tumors : 12 metastatic liver tumors, 3 hemangiomas of the liver, 2 hepatic hilar bile duct carcinomas, I carcinoma ofthe gallbladder, 1 angiomyolipoma of the liver and I HCC. No liver tumors could be detected in the other 5 NR patients. 

Methods 
The PET system (HEADTOME 111 SET-120W, Shimadzu Co., Kyoto, Japan) was used with a whole body collimator and a cyclotron with a 150 gas production system (BC-1710, Japan Steel Works, Muroran, Japan). . Details of the performance char-acteristics of this PET system and the actual methods used in the PET-study have been described in a previous report.5 The splenic blood flow per 100 g weight of the spleen (SBF) and the spleen-blood partition coefficient for water (p) were then cal-culated. The splenic volume (V) was calculated by analyzing serial splenic imagings by computed tomography (CT).6 Total splenic flow (F) was obtained as SBF x V. The indocyanine green reten-tion test at 15 min. (ICGR15), hepaplastin test (HPT), and the prothrombin elongation time (PT) were carried out in these patients. Correlations between these functional assays and splenic blood flow were then calculated. Statistical testing was per._.formed by simple regression analysis, and one-way analysis of variance (ANOVA). A p-value less than 0.05 was considered significant. 

RESULTS 

Analysis of the blood flow data is summarized in Table 1. The mean SBF and spleen-blood partition coefficient (p) of patients in the LC group were 1 17.5 ml/min/100 g and 0.824, respectively. The mean SBF and p of patients in the CH group were 102.5 ml/min/100 g and 0.702, respectively. The mean SBF and p of patients in the NR group were 160.3 ml/min/100 g and 0.770, respectively. Significant differences in SBF (p<0.01) were noted between all 3 groups, and differences in total splenic blood flow (_F) between the 3 groups were also significant (p <0.005). In addition, significant correlations were noted between SBF and V (r=-0.39, p<0.005), SBF and ICGR15 (r= -0.39, p<0.005 as illustrated in Fig. 1), SBF and HPT (r=0.37, p<0.025), p and V (r=0.36, p<0.01), p and ICGR15 (r=0.38, p<0.005), p and PT(r =0.38, p<0.01), p and HPT(r = -0.42, p<0.01) (Fig. 2), F and V (r=0.79, p<0.005), F and ICGR15 (r=0.34 p<0025). F and PT (r=0.51, p<0.005), F and HPT (r=-0.32, p<0.05), V and ICGR15 (r=0.38, p<0.005), V and PT (r=0.46, p<0.005) and between V and HPT (r= -0.33, p<0.05), these correlation coefficients being arranged in Table 2. There were no other significant correlations between any of the markers. 

DISCUSSION 

The binding of ICG to albumin after an intravenous injection was found to be rapid, with greater than 90 % of the complex being taken up by hepatocytes, followed by its subsequent removal in the bile. Thus the administration of ICG is often used to measure hepatic blood flow,7-9 and to evaluate liver function or the degree of chronic hepatic damage.10 However, we should be careful not to adopt its value if a patient has congenital ICG retention. Similarly we must take care to deal with PT because deficiency of vitamin K makes elongates prothrombin time even when there is no hepatocellular damage. In the current study, there were no patients corresponding to such special cases. HPT eliminates the inhibitory effects of proteins (induced by the absence of vitamin K) on factor X and the test reflects the ability of the liver to synthesize proteins such as prothrombin, factor VII, and factor X.11 In Owren's description of the assay,12 HPT was identified as a marker which enables the evaluation of chronic liver diseases and hepatic function.11,13 
Several conclusions are suggested by the present results. First, increasing spleen volume was due to an aggravation of hepatic function. Second, a decrease in regional splenic blood flow was accom-panied by increasing hepatic dysfunction. However, in fact, SBF in the CH group was lower than SBF in the LC group. The small number (n =6) in the CH group may contribute to the inversion of the data for the two groups, and it is possible that patients in the LC group have more chance of obtaining a venous shunt, such as a splenorenal shunt, than patients in the CH group, and so the SBF of LC becomes greater than the SBF of CH in spite of its worse liver function than that of CH. Further examination will be necessary to find the reason for this inversion. Third, total splenic blood flow does not correlate with increasing splenomegaly although an apparently significant correlation was noted between F and V. This third idea cannot be proven conclusively because the splenic volume and the total splenic blood flow could not be measured separately in our study. 
With regard to the relationship between splenic volume and various markers of liver function, the splenic volume tended to increase with the progres-sive chronic changes found in hepatic diseases; statistically significant correlations were obtained between V and ICGR15, V and PT, and V and HPT. Moreover, we noted from our analyses that F also increased significantly with advancing chronic changes when compared to the ICGR15, PT and HPT results. However, such an increase in SBF is not necessarily accompanied by an increase in V, because the relationship between SBF and V can be expressed as SBF=F/V, Therefore, SBF is not proportionate to its V. Huchzermeyerl reported that the total splenic blood flow increased as the weight of the spleen increased in spite of low specific blood flow. Furthermore, Williams2 noted that the total splenic flow calculated by intraarterial injections of radioactive xenon increased even in patients where the flow/100 g tissue was clearly reduced and Wadenvic3 reported that splenic perfusion (the percentage of total blood volume entering 100 cm3 of splenic tissue per minute) measured by intravenous injections of mln was found to decrease as the size of the spleen increased. These results were similar to our results and suggest that these increases in splenic size result from tissue expansion caused by congest-ing static blood due to portal hypertension, and from aggravating chronic changes observed in hepatic diseases. Moreover, Garnet4 reported that the spleen behaved as an arteriovenous shunt. In order to demonstrate the existence of splenic phenomena indicating an arteriovenous shunt or congestive swelling, it is necessary to determine the blood flow in the regional splenic tissue minus the fiow in the intrasplenic vascular space (real SBF). In this study, we obtained a SBF value that includes the intra-splenic vascular flow but in the future we will be developing a method for the quantification of the real SBF. PET scanning is suitable for performing such studies, because repeated measurements can be done by using 150, which has a very short half-life (123 sec). However, we analyzed the splenic blood flow by calculating an apparent SBF which included the flow in the intrasplenic vascular space, because the quantification of the real SBF was theoretically so complicated that it could not be applied clinically and the apparent SBF could be easily compared to splenic blood flow measured by other methods. In the current study, the physiologic relevance of p is not clear, but its significance may be proven if a method for the quantification of the real SBF becomes established. There are some reports record-ing the structure of splenic vessels in the case of liver cirrhosis which suggest that they are different from the vessels found in a normal liver.14,15 These difference in the structure of splenic vessels may contribute to the change in the p value. The appli-cation of PET will also solve this problem. In conclusion regional splenic blood flow is not proportionate to splenic volume, although the splenic volume increases with the progressive chronic changes characteristic of hepatic diseases. 

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