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Blood flow in auxiliary canine liver homografts
BLOOD
PIERRE
FLOW LIVER
M. CARL
G.
DALOZE, GROTH,
IN AUXILIARY HOMOGRAFTS M.D.,* M.D.,
IN 1964 Starzl et al. [9] reported that canine auxiliary liver homografts undergo progressive atrophy after transplantation in recipients reThe auxiliary ceiving immunosuppression. grafts were revascularized according to Welch’s technique [l, 111 with portal inflow provided from the lower vena cava. Subsequent studies by Marchioro et al. [4, 51 suggested that the shrinkage of the liver in the Welch preparation was due to the portalization with nonsplanchnic blood, thus depriving the liver of essential nutritional substrates. The nonanatomical revascularization could, however, affect the graft adversely also by creating an inadequate hemodynamic situation Heterotopic hepatic homografts as well as partial autografts undergo extensive atrophy when deprived of portal flow [8, lo], and the flow provided to the portal vein in the Welch preparation might be subnormal due to a low pressure gradient in the vena cava and the existence of natural collaterals. In the present study the hemodynamics of the Welch auxiliary liver was studied. From the Department of Surgery, University of Colorado School of Medicine, and the Denver Veterans Administration Hospital, Denver, Colo. *Fellow of the McLaughlin Foundation, Toronto, Canada. This work was supported by U.S. Public Health Service grants F05-TW-1154, AM 06283, AM 06344, HE 07735, AM 07772, AI 04152, FR 00051, FR 00069, AM 12148, and AI-AM-08898. Submitted for publication Nov. 24, 1967. 10
CANINE
CLAUDE AND
FRED
HUGUET, STOLL,
M.D., M.T.
METHODS Mongrel dogs weighing 10.4 to 20.9 kg. were used as recipients; nonrelated dogs 1.1 to 8.3 kg. smaller than the recipients were used as donors. Auxiliary hepatic transplants were performed with a slight modification of the Welch technique as previously described [ 91. Pentobarbital anesthesia combined with the tranquilizer phencyclidine hydrochloride was used. No immunosuppressive therapy was given after transplantation. Dogs that died of technical complications or intussusception were excluded. The patency of vascular anastomoses was established by angiography or autopsy. Blood flow in the auxiliary liver graft was studied in 10 dogs; in 5 of these the blood flow in the host liver was also measured. Flow studies were performed on the first postoperative day in all dogs; in most animals they were repeated on the third day after transplantation. HOW Studies The liver blood flow was studied in the unanesthetized state by measuring the washout of the inert radioactive gas xenon133. The procedure, which was essentially the same as that used by Hollenberg and Dougherty [3], has been described in detail in a previous report [2]. The isotope was delivered to the portal system of the auxiliary liver through a catheter
DALOZE
ET
AL.:
BLOOD
FLOW
IN
AUXILIARY
CANINE
LIVER
H~~I~GRAFTS
The FAI was studied on the first postoperative day in 7 homografts and ranged between 191 and 377 ml./min./106 gm. of tissue, with a mean value of 227. On the third day the average value in the 4 dogs in which data were obtained was 192 ml./min./lOO gm. of tissue. In 4 of the 5 experiments, in which FPI was studied in both livers, the value in the graft was higher than that in the host liver (Table 1). COMMENTS
1. Placement of catheters for delivering the Xe13” to the auxiliary liver graft and the host liver. Fig.
inserted in a vein in the hind leg, and to the arterial system through an indwelling catheter (Fig. 1). The portal system of the host liver was injected through a similar indwelling catheter. The mean flow values obtained after portal and hepatic arterial injection of the isotope (designated FPI and FAI, respectively) in normal dogs are 221 * 52 (S.D.) and 178 5 50 (SD.) ml/min./l00 gm. of tissue in our laboratory [2].
RESULTS On the first postoperative day, the FPI in the auxiliary livers ranged between 187 and 402 ml/min./l00 gm. of tissue, the mean value being 283. On the third postoperative day, the mean FPI in the 7 dogs studied was 225 ml./ min./100 gm. of tissue.
The Xel”” washout technique permits studies of blood flow in each of the 2 livers of the Welch preparation independently, and can be used in the awake animal with a minimum of manipulation. It should be emphasized, however, that flow values obtained on portal and arterial injection of Xe133 do not represent measure of fractional flow from either source. On the contrary, the presence of intrahepatic communications between the two systems [6] makes the washout of the isotope dependent on both portal and hepatic flow regardless of route of injection. Nevertheless, the fact that the FPI and FAI values differ indicates that the intrahepatic mixing is incomplete [3, 71. Hemodynamic changes caused by the nonanatomical revascularization of the auxiliary liver should be apparent immediately after transplantation. Later, the occurrence of rejection will alter the flow in the homograft [2]. The flow measurements were therefore limited to the immediate postoperative period. The flow values of the auxiliary homografts were not significantly different from those Table 1. Blood Flow Values Obtained on Portal Injection of Xenon13” in the Auxiliary Liver Homografts and the Host Livers on the First Day After Transplantation in 5 Dogs
Dog No.
Auxiliary Liver Host Liver (FPI ml./min./lOO gm. of tissue)
1
312
2 3 4 5
402 375 256 367
225 335 256 268 294 11
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
9 NO.
found previously in the liver of normal dogs [Z] . When flow was studied in both graft and host liver, the values were generally higher in the former. Thus, the revascularization of auxiliary liver grafts with Welch technique does not create an inadequate portal flow. Nonhemodynamic factors, such as, for example, those described by Marchioro et al. [4, 51, must then account for the atrophy of the graft.
1,
JANUARY
3.
4.
5.
SUMMARY The blood flow in auxiliary liver homografts revascularized according to Welch’s technique was investigated using a Xe133 washout technique. Flow measurements were taken within the first 3 days after transplantation to avoid the influence of rejection. Hemodynamic changes that could account for the atrophy occurring in this type of liver graft were not found,
6.
7.
8.
9.
REFERENCES 10. 1.
2.
12
Goodrich, E. O., Welch, H. F., Nelson, J. A., Beecher, T. A., and Welch, C. S. Homotransplantation of the canine liver. Surgery 39:244, 1956. Groth, C. G., Porter, K. A., Otte, J, B., Daloze, P. M., Marchioro, T. L., Brettschneider, L., and
11.
1~69
Starzl, T. E. Studies of blood flow and ultrastructural changes in rejecting and non-rejecting canine orthotopic liver homografts. Surgery 63:658, 1968. Hollenberg, M., and Dougherty, J. Liver blood flow measured by portal venous and hepatic arterial routes with Krss. Amer. J. Physid. 210: 926, 1966. Marchioro, T. L., Porter, K. A., Brown, B. I., Otte, J. B., and Starzl, T. E. The effect of partial portacaval transposition on the canine liver. Surgery 61:723, 1967. Marchioro, T. L., Porter, K. A., Dickinson, T. C., Faris, T. D., and Starzl, T. E. Physiologic requirements for auxiliary liver homotransplantation. Surg. Gynec. Obstet. 121:17, 1965. Rabinovici, N., and Vardi, J. The intrahepatic portal vein-hepatic artery relationship. Surg. Gynet. Obstet. 120:38, 1965. Rees, J. R., Redding, V. J., and Ashfield, R. Hepatic blood flow measurement with Xenonlss. Lancet 2:562, 1964. Sigel, B., Baldia, L. B., and Dunn, M. R. Effects of porto-systemic shunting and decreased blood flow on partial heterotopic liver autotransplants. Surg. Forum 16:288, 1965. Starzl, T. E., Marchioro, T. L., Rowlands, D. T., Kirkpatrick, C. H., Wilson, W. E. C., Rifkind, D., and Waddell, W. R. Immunosuppression after experimental and clinical homotransplantation of the liver. Ann. Surg. 160:411, 1964. Tretbar, L. L., Beven, E. G., and Hermann, R. E. The effects of portacaval shunt and portal flow occlusion on canine auxiliary liver homotransplants. Surgery 61:733, 1967. Welch, C. S. A note on the transplantation of the whole liver in dogs. Transplant. Bull. 2:54, 1955.
PIERRE
FLOW LIVER
M. CARL
G.
DALOZE, GROTH,
IN AUXILIARY HOMOGRAFTS M.D.,* M.D.,
IN 1964 Starzl et al. [9] reported that canine auxiliary liver homografts undergo progressive atrophy after transplantation in recipients reThe auxiliary ceiving immunosuppression. grafts were revascularized according to Welch’s technique [l, 111 with portal inflow provided from the lower vena cava. Subsequent studies by Marchioro et al. [4, 51 suggested that the shrinkage of the liver in the Welch preparation was due to the portalization with nonsplanchnic blood, thus depriving the liver of essential nutritional substrates. The nonanatomical revascularization could, however, affect the graft adversely also by creating an inadequate hemodynamic situation Heterotopic hepatic homografts as well as partial autografts undergo extensive atrophy when deprived of portal flow [8, lo], and the flow provided to the portal vein in the Welch preparation might be subnormal due to a low pressure gradient in the vena cava and the existence of natural collaterals. In the present study the hemodynamics of the Welch auxiliary liver was studied. From the Department of Surgery, University of Colorado School of Medicine, and the Denver Veterans Administration Hospital, Denver, Colo. *Fellow of the McLaughlin Foundation, Toronto, Canada. This work was supported by U.S. Public Health Service grants F05-TW-1154, AM 06283, AM 06344, HE 07735, AM 07772, AI 04152, FR 00051, FR 00069, AM 12148, and AI-AM-08898. Submitted for publication Nov. 24, 1967. 10
CANINE
CLAUDE AND
FRED
HUGUET, STOLL,
M.D., M.T.
METHODS Mongrel dogs weighing 10.4 to 20.9 kg. were used as recipients; nonrelated dogs 1.1 to 8.3 kg. smaller than the recipients were used as donors. Auxiliary hepatic transplants were performed with a slight modification of the Welch technique as previously described [ 91. Pentobarbital anesthesia combined with the tranquilizer phencyclidine hydrochloride was used. No immunosuppressive therapy was given after transplantation. Dogs that died of technical complications or intussusception were excluded. The patency of vascular anastomoses was established by angiography or autopsy. Blood flow in the auxiliary liver graft was studied in 10 dogs; in 5 of these the blood flow in the host liver was also measured. Flow studies were performed on the first postoperative day in all dogs; in most animals they were repeated on the third day after transplantation. HOW Studies The liver blood flow was studied in the unanesthetized state by measuring the washout of the inert radioactive gas xenon133. The procedure, which was essentially the same as that used by Hollenberg and Dougherty [3], has been described in detail in a previous report [2]. The isotope was delivered to the portal system of the auxiliary liver through a catheter
DALOZE
ET
AL.:
BLOOD
FLOW
IN
AUXILIARY
CANINE
LIVER
H~~I~GRAFTS
The FAI was studied on the first postoperative day in 7 homografts and ranged between 191 and 377 ml./min./106 gm. of tissue, with a mean value of 227. On the third day the average value in the 4 dogs in which data were obtained was 192 ml./min./lOO gm. of tissue. In 4 of the 5 experiments, in which FPI was studied in both livers, the value in the graft was higher than that in the host liver (Table 1). COMMENTS
1. Placement of catheters for delivering the Xe13” to the auxiliary liver graft and the host liver. Fig.
inserted in a vein in the hind leg, and to the arterial system through an indwelling catheter (Fig. 1). The portal system of the host liver was injected through a similar indwelling catheter. The mean flow values obtained after portal and hepatic arterial injection of the isotope (designated FPI and FAI, respectively) in normal dogs are 221 * 52 (S.D.) and 178 5 50 (SD.) ml/min./l00 gm. of tissue in our laboratory [2].
RESULTS On the first postoperative day, the FPI in the auxiliary livers ranged between 187 and 402 ml/min./l00 gm. of tissue, the mean value being 283. On the third postoperative day, the mean FPI in the 7 dogs studied was 225 ml./ min./100 gm. of tissue.
The Xel”” washout technique permits studies of blood flow in each of the 2 livers of the Welch preparation independently, and can be used in the awake animal with a minimum of manipulation. It should be emphasized, however, that flow values obtained on portal and arterial injection of Xe133 do not represent measure of fractional flow from either source. On the contrary, the presence of intrahepatic communications between the two systems [6] makes the washout of the isotope dependent on both portal and hepatic flow regardless of route of injection. Nevertheless, the fact that the FPI and FAI values differ indicates that the intrahepatic mixing is incomplete [3, 71. Hemodynamic changes caused by the nonanatomical revascularization of the auxiliary liver should be apparent immediately after transplantation. Later, the occurrence of rejection will alter the flow in the homograft [2]. The flow measurements were therefore limited to the immediate postoperative period. The flow values of the auxiliary homografts were not significantly different from those Table 1. Blood Flow Values Obtained on Portal Injection of Xenon13” in the Auxiliary Liver Homografts and the Host Livers on the First Day After Transplantation in 5 Dogs
Dog No.
Auxiliary Liver Host Liver (FPI ml./min./lOO gm. of tissue)
1
312
2 3 4 5
402 375 256 367
225 335 256 268 294 11
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
9 NO.
found previously in the liver of normal dogs [Z] . When flow was studied in both graft and host liver, the values were generally higher in the former. Thus, the revascularization of auxiliary liver grafts with Welch technique does not create an inadequate portal flow. Nonhemodynamic factors, such as, for example, those described by Marchioro et al. [4, 51, must then account for the atrophy of the graft.
1,
JANUARY
3.
4.
5.
SUMMARY The blood flow in auxiliary liver homografts revascularized according to Welch’s technique was investigated using a Xe133 washout technique. Flow measurements were taken within the first 3 days after transplantation to avoid the influence of rejection. Hemodynamic changes that could account for the atrophy occurring in this type of liver graft were not found,
6.
7.
8.
9.
REFERENCES 10. 1.
2.
12
Goodrich, E. O., Welch, H. F., Nelson, J. A., Beecher, T. A., and Welch, C. S. Homotransplantation of the canine liver. Surgery 39:244, 1956. Groth, C. G., Porter, K. A., Otte, J, B., Daloze, P. M., Marchioro, T. L., Brettschneider, L., and
11.
1~69
Starzl, T. E. Studies of blood flow and ultrastructural changes in rejecting and non-rejecting canine orthotopic liver homografts. Surgery 63:658, 1968. Hollenberg, M., and Dougherty, J. Liver blood flow measured by portal venous and hepatic arterial routes with Krss. Amer. J. Physid. 210: 926, 1966. Marchioro, T. L., Porter, K. A., Brown, B. I., Otte, J. B., and Starzl, T. E. The effect of partial portacaval transposition on the canine liver. Surgery 61:723, 1967. Marchioro, T. L., Porter, K. A., Dickinson, T. C., Faris, T. D., and Starzl, T. E. Physiologic requirements for auxiliary liver homotransplantation. Surg. Gynec. Obstet. 121:17, 1965. Rabinovici, N., and Vardi, J. The intrahepatic portal vein-hepatic artery relationship. Surg. Gynet. Obstet. 120:38, 1965. Rees, J. R., Redding, V. J., and Ashfield, R. Hepatic blood flow measurement with Xenonlss. Lancet 2:562, 1964. Sigel, B., Baldia, L. B., and Dunn, M. R. Effects of porto-systemic shunting and decreased blood flow on partial heterotopic liver autotransplants. Surg. Forum 16:288, 1965. Starzl, T. E., Marchioro, T. L., Rowlands, D. T., Kirkpatrick, C. H., Wilson, W. E. C., Rifkind, D., and Waddell, W. R. Immunosuppression after experimental and clinical homotransplantation of the liver. Ann. Surg. 160:411, 1964. Tretbar, L. L., Beven, E. G., and Hermann, R. E. The effects of portacaval shunt and portal flow occlusion on canine auxiliary liver homotransplants. Surgery 61:733, 1967. Welch, C. S. A note on the transplantation of the whole liver in dogs. Transplant. Bull. 2:54, 1955.