Changes of Hepatic Microcirculation in Acute Cholestasis

Changes of Hepatic Microcirculation in Acute Cholestasis

Takashi Osada

, Tetsuo Morishita

, Eiichi Sekizuka

, Kouji Miyazaki

, Eisuke Iwasaki

, Hiroshi Kishikawa

,

Masaru Nakano

, Tadashi Ohara

, Jiro Nishida

, Hiroshi Nagata

, and Hiromasa Ishii

Key words. Microcirculation, Liver, Cholestasis, Bile duct pressure, Portal vein

Introduction

Hepatocellular dysfunction is often seen in cholestasis and biliary obstruc- tion such as cholelithiasis and choledocholithiasis, and after endoscopic ret- rograde cholangiopancreatography (ERCP). The purpose of this study was to investigate hepatic microcirculatory changes in the increase of bile duct pres- sure experimentally.

Materials and Methods

Male Wistar rats (200–300 g) fasted overnight were anesthetized with 50 mg/kg sodium pentobarbital i.p. The common bile duct was cannulated with a Clear Vinyl Tube (o.d. 0.8 mm) and pressure was continuously meas- ured with a Pressure Monitor, PB-1 (World Instruments).

Study 1

The pressure of the bile duct was increased from basal level (+0 cmH

O) (13.7

± 2.2 cmH

O, mean ± SE, n = 7) to +10 cmH

O, +20 cmH

O, and +30 cmH

O, and kept for 6 min at each step. Systemic blood pressure was monitored

175

1

Department of Internal Medicine and Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-1-13 Sugano, Ichikawa, Chiba 272-8513, Japan

2

Saitama National Hospital, 2 Suwa, Wako, Saitama 351-0102, Japan

3

Tokyo Dental Collage, Chiba Hospital, 1-1-2 Masago, Mihama-ku, Chiba 261-8502, Japan

4

Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi,

Shinjuku-ku, Tokyo 160-8582 Japan

throughout the experiments. Blood flow at the surface of the liver was measured with a laser Doppler flowmeter, ALF2000 (Advance, Tokyo, Japan).

Blood flow in the portal trunk was measured with an Electromagnetic Blood flowmeter, MVF-3200 (Nippon Kohden, Tokyo, Japan). Microcirculation of the liver was observed using in vivo microscopy [1]. The velocity of red blood cells labeled with fluorescein isothiocyanate (FITC) in the hepatic sinusoids was measured using a high-speed video system [2] with Ektapro HS-4500 (Redlake MASD, San Diego, CA, USA).

Study 2

Rats were divided into two groups with and without increase of the bile duct pressure in the same way as study 1. Serum levels of TB, AST, ALT, LDH, ALP, GGT, and LAP were measured, and the liver was examined microscopically in both groups.

The Friedman test, Bonferroni test and Mann–Whitney U-test were used for statistical analysis. All values are expressed as mean ± SE, with P < 0.05 accepted as significant.

Results

Study 1

The mean systemic pressure (132 ± 4 mmHg at the basal level, n = 10) did not change throughout the experiment. The hepatic blood flow decreased signif- icantly (P < 0.05) from 100% ± 0% (11.8 ± 2.9 ml/min per 100 g, n = 4) at +0 cmH

O, 91% ± 2% at +10 cmH

O, 75% ± 9% at +20 cmH

O, to 54% ± 7% at +30 cmH

O (Fig. 1) during the stepwise increase of the bile duct pressure. The blood flows in the portal trunk and blood cell velocity in the hepatic sinu- soids also decreased significantly.

176 T. Osada et al.

Fig. 1. Hepatic blood flow in the increase of bile duct pres- sure. The hepatic blood flow decreased significantly (*P <

0 .05) from 100% ± 0% (mean ±

SE 11.8 ± 2.9 ml/min per 100 g,

n = 4) at +0 cmH

O during the

stepwise increase of bile duct

pressure

Study 2

There was no significant difference in the serum levels of TB, AST, ALT, LDH, ALP, GGT, and LAP between both groups. Microscopic examination did not show abnormal histological findings of the liver such as bile thrombus for- mation in the bile canaliculi, and degeneration of hepatocytes in either of the groups.

Discussion

Our study showed that increase of the bile duct pressure decreased blood flow on the liver surface and in the portal trunk, and blood cell velocity in the hepatic sinusoids without significant change of the blood chemistry and abnormal histological findings of the liver. This suggests that hepatic micro- circulatory changes are the previous step of hepatocellular dysfunction in biliary obstruction. Doppman et al. [3] reported that the liver with biliary obstruction is easily associated with infarction or abscess formation by hepatic artery ligation or embolization. The change of the hepatic blood flow might affect the prognosis of obstructive jaundice [4]. Further study on hepatic arterioles is needed.

Conclusion

The hepatic blood flow decreases with the decrease of blood cell velocity in the sinusoids and portal blood flow in acute cholestasis. This microcircula- tory change precedes the biochemical and histological changes in the liver.

References

1 . Morishita T (1997) Microcirculation of the gastrointestinal tract in acute portal hyper- tension. Microcirc Annu 13:39–42

2 . Ueki I, Sekizuka E, Okada E, et al (1993) Measurement of red blood cell velocity vector with a combination of a real-time and simultaneous multiwindows cross-correlation and high-speed video system. Bioimages 1:149–157

3 . Kodama O, Fujii Y, Tanaka T, et al (1990) Experimental and clinical studies on liver tissue blood flow in obstructive jaundice. Nippon Shokakibyo Gakkai Zasshi 87:49–56 4 . Doppman JL, Girton M, Vermess M (1982) The risk of hepatic artery embolization in

the presence of obstructive jaundice. Radiology 143:37–43

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