Immediate effects of short-term hepatic and splanchnic ischemia in pigs

Immediate Effects of Short-Term Hepatic and Splanchnic lschemia in Pigs 0. ALMERSJ6,

Temporary occlusion of the entire hepatic inflow is desirable in some surgical situations, such as exsanguinating injuries of the liver. When the hepatic inflow is occluded, the outcome will be fatal splanchnic congestion within a short time based on the fact that dogs survive splanchnic shunt or by simultaneous occlusion of the splanchnit inflow [1,3]. Total hepatic and splanchnic occlusion is generally considered relatively harmless when applied for less than fifteen minute periods. This is mainly based on the fact that dogs survive splanchnic ischemia of fifteen minutes or perhaps a little longer [I$]. Studies on the effect of splanchnic and/or hepatic ischemia are reported in the literature by Raffucci and Wangensteen [3], Drapanas et al [4], Goodall, H yn d man, and Gurd [I], Selkurt [5], Zuidema et al [6], Jolly and Foster [?‘I, Bergan et al [8], Backlund et al [9], and others. None of these studies concern the changes during and immediately after a short-term occlusion of splanchnit inflow. Also, all these studies were performed in dogs. Because of its susceptibility to outflow block, the canine liver is less suitable for experimental studies of this type: the block counteracts the normalization of circulation after ischemia. In recent years, there has been an increasing frequency of surgical experiments on the liver of pigs, particularly liver transplantations, the pig liver being very suitable for this procedure [ 1 O-1.21, especially from an immunologic point of view. Outflow block does not occur in the pig liver or in the human liver. The present study was performed to investigate From the Department of Surgery, Sahlgren Hospital, University of Glteborg, 413 45 GMeborg, Sweden. This work was supported by grant 70:69 from the Swedish Cancer Society. Reprint requests may be addressed to Dr Larsolof Hafstrbm, Sur. gical Clinic II, Sahlgrenska siukhuset. 413 45 G(lteborg. Sweden.

Volume 122, July 1971

Gijteborg,

Sweden

S. BENGMARK,

Giiteborg,

Sweden

1. DOMELLbF,

Gateborg,

Sweden

L. HAFSTRh,

GtSteborg, Sweden

in the pig some circulatory and metabolic consequences-blood pressure, pH, and potassium-of a standardized fifteen minute, simultaneous hepatic and splanchnic inflow occlusion and the immediate effects of re-establishment of the flow through these regions, Material

and Methods

Six pigs of both sexes weighing about 25 kg, about two months of age, and of Swedish land-race were used for the study. They fasted overnight, and water was restricted on the day of operation. Anesthesia was induced wilth Pentothal” which was administered intraperitoneally in a dosage of 30 mg per kg of body weight. Tracheostomy was performed. The anesthesia was continued with an equal mixture of N,O-Oi admini’stered by an Engstriim respirator. Curare was given intermittently. The abdomen was opened through a midline incision. One catheter was inserted into the femoral artery, another into the portal vein, and two into the inferior caval vein, one with the tip above the liver and the other with the tip below. The intra-arterial and intraportal pressures were continuously measured eleetromanometrically. Ringer’s solution was administered intravenously throughout the experiment. The celiac ,axis, mesenteric artery, and portal vein were occluded for fifteen minutes. Blood samples were taken from the four different catheters, that is, those in the femoral artery, portal vein, and the supra- and infrahepatic caval vein, before and fourteen minutes after occlusion, as well as five and thirty minutes after release of the occlusions. The total blood loss on each sampling was approximately 30 ml, yielding a total of 120 ml during the experiment. The samples were analyzed for hematocrit, blood sugar, electrolytes, pH, pCO,, and ~0,. Lactic acid and pyruvic acid were determined according to the method of Scholz et al [.ZS] with commercial reagents manufactured by Biochemica “Boehringer.” The result’s are given with stsandard deviation. The p values are calculated according to Student’s t test.

91

Almersj6

et al

a _

occlusion

7 _ 6

.-I______

WI....

7.3 _

‘i’_.r:.--.__... -..

7.2 _

I I I , I

7.1 70

_

-----w.

-----+__

.

_

5

_

4

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.-----D ih. covd vein a.. . . . . . . rh. cavoi

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.._

,

I ,

,

before

14

vein

.---.!..__ __ __._m _-_ -_m___-----._,,I .-...__. . ..___ i’._ ..____*_______...._..... ........* . -._ D I __-_. - o_ - - -’ I

min

occlusion

, 5

30 m,n, offer

ml,“.

before

re,eo*e

I 14 min. occlusion

5 m,n.

30 n in offer

release

Figure 1. pH changes in arterial, portal, and supra- and infrahepatic caval vein blood during and after fifteen minutes’ occlusion of celiac axis, superior mesenferic artery, and portal vein.

Figure 2. Potassium concentration (mEq/L -C SD) in are terial, portal, and supra- and infrahepafic caval vein blood during and after fifteen minutes’ occlusion of celiac axis, superior mesenferic artery, and portal vein.

Results

Sodium and chloride levels were unchanged throughout the study. A significant increase in the potassium concentration (Figure 2) was seen during occlusion in the blood from the suprahepatic caval vein, and a smaller but statistically significant increase was noted in farterial and portal blood. The difference between the infra- and suprahepatic caval vein potassium concentration during occlusion was statistically significant. Five minutes after re-establishment of the circulation, the potassium concentration in the portal and infrahepatic caval blood was further increased. An increasing lactic acid ooncentration (Figure 3) was observed throughout the experiment. During occlusion it rose significantly in the supra- and infrahepatic caval vein blood. After re-establishment of circulation, it was significantly raised in the arterial and portal blood. Pyruvic acid increased significantly in arterial and in suprahepatic caval vein blood during OCelusion. (Figure 4).

In three pigs, the arterial pressure fell instantly upon release of the occlusion; in three others, it fell more slowly. The portal pressure showed a slight increase in two pigs (9 > 11 mm, 9-15 mm Hg). It returned to preocclusion levels after the release. Hematocrit was at a constant level during and after the occlusion and blood sugar level did not change significantly during and after the occlusion. The oxygen saturation remained unchanged during the period of occlusion and after re-establishment of flow. There were no changes in pH during the period of occlusion. The re-establishment of circulation was followed by a statistically significant decrease to a mean of 6.99 in the portal blood. The decrease to 7.07 in the suprahepatic caval vein blood was not statistically significant (0.10 > p > 0.05). (Figure 1.) The pC0, was significantly lowered from 38+5 to 26 +- 2 mm Hg in the arterial blood during occlusion. The re-establishment of the circulation did not influence the pC0,. TABLE I

Rapid changes appear within the cells during

pH Changes (See Figure 1) Before _~...~

At Release of Occlusion

Occlusion Artery Portal vein lnfrahepatic Suprahepatic

TABLE II

caval vein caval vein

7.44 7.32 7.35 7.32

f zt f zk

0.12 0.16 0.13 0.14

(6) (5) (6) (6)

7.45 7.17 7.31 7.24

Ilt zt -Ir f

0.14 0.13 0.16 0.19

(6) (6) (6) (6)

Five Minutes after Release 7.33 6.99 7.17 7.07

z!z 0.10 (6) zk 0.12 (6) ziz 0.21(6) zk 0.18 (6)

Thirty Minutes after Release 7.33 7.07 7.20 7.14

zkz 0.14 f 0.17 f 0.18 z!z 0.17

(5) (5) (5) (5)

Potassium Concentration (See Figure 2) At Release of Occlusion

Before Occlusion Artery Portal vein lnfrahepatic Suprahepatic

92

Comments

caval vein caval vein

4.3 4.4 4.5 4.5

f f zk f

0.5 0.7 0.8 1.3

(6) (5) (6) (6)

5.6 f 5.8 f 5.1 zk 7.2 zt --__

1.5 1.5 0.5 1.3

(6) (6) (6) (6)

Five Minutes after Release 6.9 7.7 6.8 8.0

LIZ 1.3 f 1.9 zt 1.7 z!z 1.6

(6) (6) (6) (6)

Thirty Minutes after Release 6.9 6.8 7.2 7.4

The American

f * f *

1.4 1.7 1.5 1.5

(5) (5) (5) (5)

Journal

of Surgery

Hepatic

and Splanchnic

&hernia

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I

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I

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.

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4.

0-.-

’

por10,

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I

I

14 min. occlusion

5min

30mtn

offer

re,eose

Figure 3. Lactic acid concentration (mM/L -+: SD) in arteriaf, portal, and supra- and infrahepatic caval vein blood during and after fifteen minutes’ occlusion of celiac axis, superior mesenteric artery, and portal vein.

occlusion of vascular inflow. Barn&t, Turner, and Walker [14] found that the pH of the liver dropped to 6.84 in fifteen minutes of hepatic inflow occlusion. The changes taking place intracellularly are known to be reflected in the circulation within a short period, in the portal blood, in the hepatic venous blood, and in the systemic blood. Occlusion of the hepatic circulation for periods varying from sixty to 120 minutes has been found to be followed by an increased release of potassium from the liver to the circulation [7,9,15]. An increasing lactic acid concentration and a decrease in pH has also been observed [9]. Temporary occlusion of the intestinal arterial circulation without any occlusion of the hepatic artery is known to be sufficient to induce severe metabolic changes within a short period. Thus, Robertson, Lyall, and Macrae [16] reported an increased acidosis after release from temporary (mean 130 minutes) superior mesenteric artery occlusion, This acidosis was associated with increase in portal and systemic venous potassium and a decrease in arterial pressure. TABLE III

Artery Portal vein lnfrahepaticcavalvein Suprahepatic cavalvein

2.9zt 1.0(6) 3.6f 2.0 (6) 3.1 zt 2.0 (6) 2.4 z!=0.9(5)

5 msn.

30 min. after

reldose

Figure 4. Pyruvic acid concentration (mM/L _t SD) in arterial, portal, and supra- and infrahepatic cavaf vein blood during and after fifteen minutes’ occlusion of celiac axis, superior mesenteric artery, and portal vein.

In the present study, a rise was registered during occlusion in potassium in suprahepatic caval venous blood and in arterial and portal venous blood ; in lactic acid in supra- and infrahepatic caval venous blood ; and in pyruvic acid concentration in arterial and suprahepatic caval venous blood. It is possible that these increases might be due to several factors, such as leakage from an ischemic splanchnic region thrqugh venovenous or venolymphatic anastomosis, or an ebbing flow through the open hepatic veins. The present study shows that acid products and potassium are released from the ischemic splanchnit organs and pass through the portal vein to the liver after a normothermic occlusion of fifteen minutes. Thus, the pH was 6.99, pC0, 75 mm Hg, lactic acid concentration 7.9 mM per L, and the potassium concentration 7.8 mEq/L in the portal blood five minutes after the release of the occlusion. The liver cannot immediately eliminate these products. Thus, the lactic acid concentration increased in arterial blood after re-establishment of the circulation. Increased serum lactic acid levels can also be obtained by means other than hypoxia, such as, by

At Release of Occlusion

FiveMinutes afterRelease

3.8 zt 1.0(6) 4.9rt 2.3(6) 5.5 f 2.1(6) 5.0 f 2.4(5)

6.3zk 1.7(6) 7.9zt 2.5(6) 6.4 f 2.9(6) 7.0x!=2.7 (5)

At Release ofOcclusion

FiveMinutes afterRelease

ThirtyMinutes afterRelease 7.2 * 9.0 f 7.0 * 7.3zt

3.5(5) 2.6 (4) 2.9(5) 3.2 (5)

Pyruvic Acid Concentration (See Figure 4) Before Occlusion

Artery Portalvein lnfrahepaticcavalvein Suprahepaticcavalvein

Volume

I

14 min. occlubion

Lactic Acid Concentration (See Figure 3) Before Occlusion

TABLE IV

I

before

I ,

1

before

-.-a

122, July 1971

0.16 + 0.04(6) 0.16 =k 0.07(6) 0.14 zk 0.07 (6) 0.13 f 0.04(6)

0.20 f 0.19f 0.2Ozt 0.22xk

0.04(6) O.OS(6) 0.09(6) 0.08(6)

0.24 dz 0.08(6) 0.22 f 0.06(6) 0.23& 0.08 (6) 0.2Ozk 0.08(6)

ThirtyMinutes afterRelease 0.28=!=0.12(5) 0.27 zk 0.07 (5) 0.27 It 0.13(5) 0.20 f: 0.08(5)

93

Almersjij

et al

a lowered pC0,. The moderate decrease of pCOn to 26 mm Hg can only to a minor extent be responsibIe for the increase in lactate during the occlusion period [l7]. This study shows that the homeostasis is already influenced during fifteen minutes of splanchnic and hepatic ischemia. These changes further increase after re-establishment of the circulation and the wash-out of stagnant products. These products cannot be immediately buffered or metabolized in the liver, but will influence the general circulation and result in hypotension or vascular collapse. It therefore seems important in clinical practice to compensate for these changes during both hepatic and splanchnic ischemia, and especially during revascularization of these regions. It can be concluded that a simultaneous normothermic occlusion of the s,planchnic and hepatic circulation in the pig for fifteen minutes is sufficient to result in hyperkalemia during this period, and acidosis and increased hyperkalemia immediately after. Summary

The superior mesenteric artery, celiac artery, and portal vein were occluded for fifteen minutes in a series of pigs. The pC0, level was lowered in arterial blood during the period of occlusion. Potassium increased in suprahepatic caval venous blood, and also in arterial and portal venous blood during that period. Lactic acid increased in supraand infrahepatic caval venous blood and pyruvic acid in arterial and suprahepatic caval venous blood. After re-establishment of circulation, the arterial pressure fell. A decrease of pH to 6.99 was measured in portal venous blood. Potassium increased in portal venous and infrahepatic caval venous blood and lactic acid in arterial and portal venous blood after re-establishment of circulation.

94

References 1. Goodall RGW, Hyndman WWB, Gurd FN: Studies on hypothermie in abdominal surgery. Arch Surg 75: 1011, 1957. 2. Johnstone FRC: Acute ligation of the portal vein. Surgery 41: 958, 1957. 3. Raffucci FL, Wangensteen OH: Tolerance of dogs to occlusion of entire afferent vascular inflow to the liver. Surg Forum 1: 191, 1951. 4. Drapanas T, Becker DR, Alfano GS, ‘Potter WH, Stewart JD: Some effects of interrupting hepatic blood flow. Ann Surg 142: 831, 1955. 5. Selkurt EE: Intestinal ischemic shock and the protective role of the liver. Amer J fhysiol 197: 281, 1959. 6. Zuidema GD, Turcotte JG, Wolfman EF Jr, Child CG: Metabolic studies in acute small-bowel ischemia. Arch Surg 85: 146, 1962. 7. Jolly PC, Foster JH: Hepatic inflow stasis. Surgery 54: 45, 1963. 8. Bergan JJ, Gilliland V, Troop C, Anderson MC: Hyperkalemia following intestinal revascularization. JAMA 187: 17, 1964. 9. Backlund WM, Stevens TJ, Hamit CHF, Jordan GL: Hepatic ischemia in dogs. JAMA 194: 1116, 1965. 10. Peacock JH, Terblanche J: Orthotopic homotransplantation of the liver in the pig, p 333. The Liver (AE Read, ed.) London, Butterworth, 1967. 11. Calne RY, White HJO, Yoffa DE, Maginn RR, Binns RM, Samuel JR, Molina VP: Observations of orthotopic kver transplantation in the pig. Brit Med J 2: 478, 1967. 12. Calne RY, Whlite HJO, Yoffa DE, Binns RM, Maginn RR, Herbertson RM. Millard PR. Molina VP. Davis DR: Prolonged survival of liver transplants in the pig. Brit Med J 4: 645,1967. 13. Scholz R, Schmitz H, Bucher TH, Lampen JO: Uber die Wirkung von Nystatin auf Backerhefe. Biochem 331: 71, 1959. 14. Barnett WO, Turner MD, Walker JW: The effects of afferent circulato’ry arrest upon hydrogen ion concentration of the liver. Surg Gynec Obstet 106: 511, 1958. 15. Stewart JD, Potter WH, Hubbard RS, Andersen MN: Potassium movement in acute liver damage. Ann Surg 138: 593,1953. 16. Robertson GS, Lyall AD, Macrae JGC: Acid-base disturbances in mesenteric occlusion. Surg Gynec Obstet 128: 15, 1969. 17. Eldridge F, Salzer J: Effect of respiratory alkalosis on blood lactate and pyruvate in humans. J Appl Physiol 22: 461, 1967.

The American

Journal

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