Title Hepatic Hemodynamics and Arterial Ketone Body Ratio inpatients with chronic liver deseases( Dissertation_全文 )

Author(s) Kajimura, Kozo

Citation Kyoto University (京都大学)

Issue Date 1993-09-24

URL https://doi.org/10.11501/3070354

Right 本文は出版社の許諾条件により公開していません

Type Thesis or Dissertation

Textversion author

Kyoto University

9 〈プ

Hepatic Hemodynamics and Arterial Ketone Body Ratio

in patients with chronic liver deseases

(慢性肝障害患者における肝血行動態と動脈血中ケトン体

比に関する研究)

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Transcatheter Hepatic Arterial Drug Infusion Therapy for

Hepatocellular Carcinoma

Effect on the .Arterial Ketone Body Ratio

K. KAJ!\HjRA, F. ~10RfY.-\SU. H. SOMEDA.~L OKL.i\1.-\ . K. ~10Ri & K. OZ.-\ \\ 'A First Depc. of lntern2l Medicine. and Second Dc:pt. of Surgery. Facul;y of .\kd icine.

1i,·ersity. Kyoro. J<:!pan

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Kajimura K, \1oriyasu F.Someda H. Okur.1a \1, Mori i-:. 0:2.w2 K. TransC2thetcr hepatic aneri2.l drug infusion theraov for :.e~~ltulu orcinoma . Effect on the arterial ketone bodv ratio. Scand J • . /, r--·-, . .

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The arterial ketone body ra•io (acetoacet2te to t)-hycroxybu::·rate) " ·as me2s•..tred in 15 pa·ients with chronic liver disease ~fore and 2fter the infusion of a:1:ic::nce r drugs or embolic agents (gelatin sponge or iodized oil) into the hepa!ic artery. The arterial keton~ body ra:io decreased a[ter hepatic angiography and decreased further at 15 min after infusion ther2.py. When the arterial ketone body ratio decreased to 1.0 or less on at least one occasion a:ter infusion therapy. the ratio af;er hepatic angiography was always 1.35 or less. Such patients de,·eloped m.:;rked systemic symptoms like fe\'er and severe liver dysfunction . . -\scites also de,·eloped in three patients in whom the arterial ketone bod:· ratio was reduced to 0.7 or less at 24 h after infusion thera;:>y. The arterial ke:one ~ody ratios improved at 3-7 days after iniusion therapy. In the seven patients treated with gelatin sponge embolization, the rat io at 3-7 days after therapy was actually higher than that before angiography .

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~ Key words: Arterial ketOne body ratio: ;edox: transcathe:er :::·erial embolization

Fuminori .A.foriyasu. :\!.D., First Dept. of :'vfedicine, Facu!:;; of .\fedicine, Kyoto Uniuersiry, 5-1 Shogoin­Ka"·aharacho, Sakyo·ku, Kyoto. 606. Jcpc.n

The infusion of various drugs into the hepatic artery is currently widely used in the diagr10sis and treatment or' li,·er tumors. In particular, transcatheter arterial embolization (TAE) plays a major role in the treatment of patients unable to undergo surgery for primary hepatocellular carcinoma (1, 2). This is because normal liver cells recei,·e a dual blood supply from the portal vein and hepatic artery, while hepatocellular carcinoma cells receive most of their blood supply from the! hepatic artery (3). However, in patients with advanced liver cirrhosis or with tumor infiltrating the portal vei n, hepatic failure after drug infusion can be a problem, and death due to hepatic insufficiency has also been reported (1) . However, no definitive guidelines are yet available to determine whether it is s2.fe to ir1fuse drugs into

the hepatic artery. According to the redox theory proposed by Ozawa et al.

(~-6), the arte rial ketone body ratio (AKBR; acetoacetate to ,6-hydrox:ybutyrate) indicates both hepatic mitochondrial function and the hepatic functional reserve because it is proportional to the hepatic energy charge. In this study we measured the A KB R before and after the infusion of drugs into the hepatic artery, to determine whether it was a usdul ,·ariable for predicting posttreatmen hepatic insufficiency.

PATIENTS A '\10 \.fETHODS

The subjects , .. ,.ere 15 patients ,,,.ith chronic li,·er disease .

Their clinical ;Jrofi!es. diagnoses. indocyanine green test ([CG-K) ,·a!ues, and treatmen:s are shown in Table I. In pa•ients with li,·er cirrhosis (LC) and chronic hepatitis (CH) the diagnosis ,;.·as based on liver biopsy, laparoscopy, angio­graphy, and laboratory data. Informed consent to participate in this study was obtained from all patients.

Angiography of •he celiac artery, common hepatic artery, and superior mesenteric artery was performed by the Sel­dinger method. After arteriography, hepatic venography v.:as performed using a 7 Fr occlusion balloon catheter (\fedi­tech , Inc., Watertown. \1ass., USA.), which 'vas introduced into the hepa,ic ,·ein \'ia the femoral veiil. A volume of 1~0-160 ml of contrast medium (Iopamiron~, Schering AG, Berlin, Germany) was injected for angiography. Drugs and/ or embolic agents were then injected into the common hepatic a!lery, proper hepatic artery, right hepatic artery, or ldt hepatic utery via a catheter. The drugs and embolic agents included mitomycin C (Mitomycin-S~; Kyoma Hakko Kogyo, Tokyo. Japan), 5-Auorouracil (5-FU~; F. Hoffmann­La Roche, Basel, Switzerland), doxorubicin hydrochloride (Adriacin~; Farmitali2. Carlo Erba, Milano. Italy), iodized oil (Lipiodoi'E; Andre Guebert. Aulnay-Sous-Bois Cedex. France). and gelatin sponge (Sponzel'i; Yamanouti, Tokyo Japan). The doses of iodized oil, mi omycin C, 5-A uo

rouracil. and do.\orubi::in hydrochloride were 5-10 m!, 10-20 mg. 250 mg , and 10-.30 mg. respectively. Half to a whole · gelatin sponge bloch: was used. ,,·ith the sponge being cu

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Effect of dobutamine on the arterial ketone body ratio and portal blood flow velocity In cirrhosis

Kajimura K. Moriyasu F, Kimura T, Okuma M, i\·1ori K, Ozawa K. Effect of dobutamine on the arterial ketone body ratio and portal blood now \·elocity in cirrhosis .

Abstract: We studied the relationship between the portal blood now velocity and the arterial ketone body ratio in patients with chronic liver disease receiving a dobutamine infusion. \Ve used an ultrasonic Doppler duplex system to evaluate the portal blood now velocity. Dobutamine was gi\·en intravenously at 5 j.lg/kg/ min for 20 min. Dobutamine infusion induced smaller changes in the portal blood no\\· velocity and ketone body ratio in liver cirrhosis than in chronic hepatitis. The existence of shunts and the poor increase of the cardiac index in response to dobutamine explained the limited improvement of portal blood now velocity in cir­rhosis patients. The ketone body ratio was improved by dobutamine in cirrhosis patients whose portal blood now velocity was increased by more than I 0%, while this ratio decreased when the increase of it \l.:as less than I ou;.,. There was no change in portal oxygen extraction in the cirrhosis group, and portal oxygen uptake only increased \v·hen the portal blood now ,·elocity rose by mo re than I 0%. Dobutamine should only be used to treat liver failure if the portal blood now velocity is increased by more than I 0% or the arterial ketone body ratio is improved by a test infusion.

A bbr1!1·iat inns usc:d in this papa: A K B R (arterial ketone body ratio), CH (chronic hepatitis), CI (cardiac index), FHVP (free hepatic venous pressure), POE (portal oxygen extraction), POU (portal oxygen uptake), LC (liver cirrhosis), PBFY (portal blood now velocity), WHYP (wedged hepatic venous pressure).

Kozo Kajimura 1, Fumlnorl Moriyasu 1,

Tohru Kimura 1, Minoru Okuma 1,

Keiichlro Morl 2 and Kazue Ozawa 2

'First Department of Internal Medicine. Fccutty ol Medicine and 1Second Department ol Surgery, Fccul\y of Medicine. Kyoto University. Kyoto. Japan

Key words: arterial ketone body ratio - dobutam­ine - hepatic hemodynamics - portal blood flow velocr.y - redox

/1 Fuminori r'IORIY

11ASU. M.D.. First Department of

Medicine. Facutty of Medicine. Kyoto UniversiTy. 54 Shogoin-Kawaharacho. Sakytrku. Kyoto, 606. Japan

Received 30 June 1992. accepted for publicction 25 January 1993

Since the liver consumes an enormous amount of energy in order to carry out its various functions. the energy-producing capacity of hepatic m ito­chondria may be said to represent the hepatic func­tional resen-c. The hepatic ketone body ratio (acetoacetatc i ~-hydroxybutyrate) is normally in equilibrium ,,·ith the ratio of the oxidized and re­duced forms of free nicotinamide adenine dinucleo­tide (free NAD • /NADH ratio) in the mitochon­dria (1). Since ~1cero:...~cetate and 0-hydroxybut)T<lt ' can pJ ss freely ~Kross the cell membr~1ne. <.md since there is 3 close relationship between the ketone body r·:Jtio of hepatic ,·enous bl ood ~1nd th:H of arter i:1 l blood. the arterial ket o ne bod y LJ.t ll"'

(.-\KBR) renccts the hepatic miroch o ndr i ~tl ;·l dO \

state (2. 3). E,·idencc has been accumulating that the A K BR is an accurate parameter for evaluating hepatic function (4) and is related to the metabolic basis of multiple organ fJilure (5). In addition. the metabolic aspects of chronic liver disease have recently been analyzed by investigating diurnal nuctu:J.tions of the .-\KBR and the blood glucose le,·cl (6) .

HepJtic blood no"· has J close correlation with the hepJtic ATP k\cl (7. S) . The cellular le,·el of ATP decrease s rap id ly in ischemi c li,-cr. anJ inte r­ruption of hepJtic bl ood ll o ,,· cwses a reduction i r1 t he ,.; K B R d u e t (\ in h i bit i 0 n 0 r the 0 Xi d 3 t i 0 n 0 f \' . .;OH ,· i:l m itochond r i:ll oxidative phosphoryla­t!O I1. C~tt ech o l a m i n cs innuu1ce hcpJtic blood now.