Biomaterials, Artificial Cells and Immobilization Biotechnology
ISSN: 1055-7172 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ianb18
Modified Hemoglobin Solution as Possible Perfusate Relevant to Organ Transplantation T Agishl, K Sonda, I Nakajlma, S Fuchinoue, H Honda, H Suga, H Liu, S Teraoka & K Ota To cite this article: T Agishl, K Sonda, I Nakajlma, S Fuchinoue, H Honda, H Suga, H Liu, S Teraoka & K Ota (1992) Modified Hemoglobin Solution as Possible Perfusate Relevant to Organ Transplantation, Biomaterials, Artificial Cells and Immobilization Biotechnology, 20:2-4, 539-544, DOI: 10.3109/10731199209119680 To link to this article: http://dx.doi.org/10.3109/10731199209119680
Published online: 11 Jul 2009.
Submit your article to this journal
Article views: 3
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ianb18 Download by: [University of California Santa Barbara]
Date: 04 April 2016, At: 00:37
BIOMAT., ART. CELLS
&
IMMOB. BIOTECH., 20(2-4), 539-544 (1992)
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
MODIFIED IIlMOCLOBIN SOI.UTION AS POSSIB1.E PERFUSATE RELEVANT TO ORGAN TRANSPIANTATION
Agishi T. Sonda K , Nakajlma I , Fuchinoue S Honda 11, Suga H , Liu H, Teraoka S & Ota K Dcpt of Surgery, Kidney Center Tokyo Womcn's Medical College 8-1 Kawada-cho. Shlnjuku-ku. Tokyo 162. Japan ABSTRACT
A modifled hcmoglobin solution ( conjugate solutlon. PHP solution) has very interesting characteristics such as oxygen-carrying property without corpuscular components. Experimental use of the PllP solution has shown promissing posibilities as a perfusate relevant to organ transplantations. 1)Elongatlon of warm ischemic time in canine kldneys : Dogs survlvcd even with the unilateral kldneys whlch had been exposed up to 4 . 5 hour warm ischemia and. thereafter, perfused wlth the PlIP solution. 2)Elongation of perfusion preservation period of canine livers : Dogs survived with the transplanted livers whlch had been perfused for 48 hours with the PtlP solution. 3)Successful pcrfusion of rat small Intestine : Lewis rat intestines perfused and preserved for 12 hours with the PHP solution showed a higher survival rate compared wlth those with Collins or UW solution. 4)Removal of antibodies : By exchange transfusion with a total of 30 - 60 ml of the PHP solution. a Lewls rat hematocrit lowered to 5 % while IgG went down to nil from 8970 mg/dl. IgA to 28 mg/dl from 118 mg/dl and 1gM to 190 mg/dl from 897 mg/dl. This technique is expected to be applicable for removal of the naturally exlsting antlbodies in xenotransplantation. A modified hemoglobin solution ( congugate, PHP solution, supplied from a research group of artificial blood, the Ministry of Welfare of Japan and produced t y Ajinomoto C o . Inc.. Tokyo, Japan) has vcry interesting characteristics such as oxygen-carrying property without corpuscular components. Usefulness and safety of the currently available PHP solution for supplementation or replacement fy5)whole blood have been reported elsewhere in animal models . It has been our concern to search possible applications of the PHP solution for other than mere supplementation. Reported herein is a summarized description of our experimental results of applications of the PHP solution as a perfusate relevant to organ transplantations.
539 Copyright 0 1992 by Marcel Dckkcr. Inc.
540
AGISHI ET AL.
ischemia 4.5hrs 4hrs 3hrs (1)
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
mgldl
3hrs (2)
11. 10 * 9.
-
---6--
-----
a7654-
321V
0
5
10
15
20
days
after renal ischemia
Fig.1 Change in S-creatinine level after renal ishemia and PllP solution infusion
1)Elongation of warm ischemic time in canine kidneys : The remaining renal artery of the unilaterally nephrectomixed dogs was clamped for different periods at a room temperature. 5 0 0 ml of the PHP solution was infused immediately after declamping. Dogs survived long even after up to 4 . 5 hour warm renal ischemia even with temporarily impaired kidney function. Recovery in renal blood flow immediately after declamping was remarkably faster in the PH solution infusion animals than no treatment animals (Fig. 1) .
5)
Post-ischemic infusion of the PHP solution is expected to ameliorate ischemic renal tubular necrosis and retrieve faster the graft function in kidney transplantation. 2)Elongation of perfusion preservation period of canine livers : Orthotopic liver transplantations have been done in mongrels. Garaft livers were preserved with perfluorochemical-containing perfusates or PHP-containing perfusates on a perfusion preservation machine at 4 degree centigrade for different periods. Consciousness recovered in 4 out of 10 dogs transplanted
541
MODIFIED HEMOGLOBIN SOLUTION A S PERFUSATE
%
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
=5
\
\
\
---
\ \
\
twenty-four-hour preservation (n= 5 )
\
forty-eight-hour preservation
\
(n=10)
\n=4
\
\
hr
12hr
24 hr
2 days
7days
Time
Fig.2 Survivals with transplantated livers after perfusion preservation with PHP solution
with the grafts preserved for 24 hours with perfluorochemicalcontaining perfusates compared to 7 out of 8 dogs with the PIW solution. Of these, one of 5 dogs with the grafts perfused with the PHP solution containing high Na. high K and bicarbonate survived long. Furthermore, 4 of 10 dogs receiving the grafts n recovcrcd preserved for 48 hours with this particular compos consciousness and survived up to 2 days ( Fig. 2 ) . 3)Successful perfusion of rat small intestine : Small intestine transplantations have been done between Lewis rats. Intestinal grafts were preserved for different periods after irrigation of the vascular bed with Collins solution, University Wisconsin solution or the PHP solution at 4 degree centigrade. For the latest, contlnuous irrigation of the
iM
542
A G I S H I ET A L .
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
Smal I Intestine Transplant at ion survival 1 4 ws after Tx survival (24ws) out of 6+ 7-
6
Preservation period (brd
12 24
654-
32-
1-
Group I Fig.3
Col I ins Group II
uw
PHP
Group Ill
GrouplV
solution
Survivals with transplanted small intestine after preservation with Collins. UW or PHP solution
intestinal lumen with the PHP solution bubbled with oxygen gas was added. Five of 6 animals transplanted with the grafts preserved for 12 hours with the PHP solution survied f o r longer than 4 weeks while only 3 of 6 survived in other groups. There was no difference among the groups transplanted with the grafts preserved for 6 or 24 hours ( Fig. 3 ) . 4)Removal of antibodies : Exchange transfusion used to be clinically applied as a treatment modality f o r removal of ABO or Rh mismacch antibodles. Animal experiment showed availability, efficacy and safety of the PHP solution as a transfusate in new type of exchange transfusion. whole body rinse-out$ 1 . The PHP solution was tnvestigated for applicability as a transfusate to remove antibodies. Exchange transfusion was done in Lewis rats with 30 -
MODIFIED HEMOGLOBIN SOLUTION AS PERFUSATE
543
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
Exchange Transfusion with PHP Soluion -reduction in Igs-
25%
Time Fig.4
Reduction in immunoglobulins after exchange transfusion with PHP solution
60 ml of the PHP solution as transfusate. IgG decreased to 0 % to
an initial value immediately after exchange transfusion, IgA decreased to 24 t and IgM decreased to 21 %. and gradually recovered to a pretreatment level until 14th day. This technique is expected to be specially applied for removal of the naturally existing antibodies in xenotransplantation in order to prevent hyperacute rejection crisis which may occur immediately after transplantation with a very high incidence of irreversibllity ( Fig. 4 ) . REFERENCES 1)Matsushita Y. Iwashita Y. Iwasaki K et al. Physiologic effects of pyridoxylated-hemoglobin-polyethyleneglycol conjugate solution in exchange transfusion. Trans h e r SOC Artif Intern Organs 32:490-494.1986.
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
544
AGISHI ET AL.
2)Agishi T, Funakoshi Y, Honda H et al.(Pyridoxylated hemoglobin)-(polyoxyethylene) conjugate solution as blood substitute for normothermic whole body rinse-out. Biomaterials, Artificial Cells and Artificial Organs 16(1-3):261-270.1988. 3)Sonda K. Agishi T. Suzukl T et al. Amelioration of renal ischemic damage by perfusion with stabilized hemoglobin solution. Jpn J Artif Organs 18(1):361-364.1889. 4)Fuchinoue S . Agishi T, Nakajima I. et al. Evaluation of (pyridoxylated hemoglobin)-(polyoxyethylene) conjugate solutlon as perfusate for liver preservation. A S A I O Transactions 33(3):390-394.1987. 5)Nakajima I. Fuchinoue S . Agishi T. et al. Twenty-four-hour liver preservation using artificial blood substitutes. Transplantation Proceedings 2O(Suppl 1):942-944.1988.
ISSN: 1055-7172 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ianb18
Modified Hemoglobin Solution as Possible Perfusate Relevant to Organ Transplantation T Agishl, K Sonda, I Nakajlma, S Fuchinoue, H Honda, H Suga, H Liu, S Teraoka & K Ota To cite this article: T Agishl, K Sonda, I Nakajlma, S Fuchinoue, H Honda, H Suga, H Liu, S Teraoka & K Ota (1992) Modified Hemoglobin Solution as Possible Perfusate Relevant to Organ Transplantation, Biomaterials, Artificial Cells and Immobilization Biotechnology, 20:2-4, 539-544, DOI: 10.3109/10731199209119680 To link to this article: http://dx.doi.org/10.3109/10731199209119680
Published online: 11 Jul 2009.
Submit your article to this journal
Article views: 3
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ianb18 Download by: [University of California Santa Barbara]
Date: 04 April 2016, At: 00:37
BIOMAT., ART. CELLS
&
IMMOB. BIOTECH., 20(2-4), 539-544 (1992)
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
MODIFIED IIlMOCLOBIN SOI.UTION AS POSSIB1.E PERFUSATE RELEVANT TO ORGAN TRANSPIANTATION
Agishi T. Sonda K , Nakajlma I , Fuchinoue S Honda 11, Suga H , Liu H, Teraoka S & Ota K Dcpt of Surgery, Kidney Center Tokyo Womcn's Medical College 8-1 Kawada-cho. Shlnjuku-ku. Tokyo 162. Japan ABSTRACT
A modifled hcmoglobin solution ( conjugate solutlon. PHP solution) has very interesting characteristics such as oxygen-carrying property without corpuscular components. Experimental use of the PllP solution has shown promissing posibilities as a perfusate relevant to organ transplantations. 1)Elongatlon of warm ischemic time in canine kldneys : Dogs survlvcd even with the unilateral kldneys whlch had been exposed up to 4 . 5 hour warm ischemia and. thereafter, perfused wlth the PlIP solution. 2)Elongation of perfusion preservation period of canine livers : Dogs survived with the transplanted livers whlch had been perfused for 48 hours with the PtlP solution. 3)Successful pcrfusion of rat small Intestine : Lewis rat intestines perfused and preserved for 12 hours with the PHP solution showed a higher survival rate compared wlth those with Collins or UW solution. 4)Removal of antibodies : By exchange transfusion with a total of 30 - 60 ml of the PHP solution. a Lewls rat hematocrit lowered to 5 % while IgG went down to nil from 8970 mg/dl. IgA to 28 mg/dl from 118 mg/dl and 1gM to 190 mg/dl from 897 mg/dl. This technique is expected to be applicable for removal of the naturally exlsting antlbodies in xenotransplantation. A modified hemoglobin solution ( congugate, PHP solution, supplied from a research group of artificial blood, the Ministry of Welfare of Japan and produced t y Ajinomoto C o . Inc.. Tokyo, Japan) has vcry interesting characteristics such as oxygen-carrying property without corpuscular components. Usefulness and safety of the currently available PHP solution for supplementation or replacement fy5)whole blood have been reported elsewhere in animal models . It has been our concern to search possible applications of the PHP solution for other than mere supplementation. Reported herein is a summarized description of our experimental results of applications of the PHP solution as a perfusate relevant to organ transplantations.
539 Copyright 0 1992 by Marcel Dckkcr. Inc.
540
AGISHI ET AL.
ischemia 4.5hrs 4hrs 3hrs (1)
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
mgldl
3hrs (2)
11. 10 * 9.
-
---6--
-----
a7654-
321V
0
5
10
15
20
days
after renal ischemia
Fig.1 Change in S-creatinine level after renal ishemia and PllP solution infusion
1)Elongation of warm ischemic time in canine kidneys : The remaining renal artery of the unilaterally nephrectomixed dogs was clamped for different periods at a room temperature. 5 0 0 ml of the PHP solution was infused immediately after declamping. Dogs survived long even after up to 4 . 5 hour warm renal ischemia even with temporarily impaired kidney function. Recovery in renal blood flow immediately after declamping was remarkably faster in the PH solution infusion animals than no treatment animals (Fig. 1) .
5)
Post-ischemic infusion of the PHP solution is expected to ameliorate ischemic renal tubular necrosis and retrieve faster the graft function in kidney transplantation. 2)Elongation of perfusion preservation period of canine livers : Orthotopic liver transplantations have been done in mongrels. Garaft livers were preserved with perfluorochemical-containing perfusates or PHP-containing perfusates on a perfusion preservation machine at 4 degree centigrade for different periods. Consciousness recovered in 4 out of 10 dogs transplanted
541
MODIFIED HEMOGLOBIN SOLUTION A S PERFUSATE
%
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
=5
\
\
\
---
\ \
\
twenty-four-hour preservation (n= 5 )
\
forty-eight-hour preservation
\
(n=10)
\n=4
\
\
hr
12hr
24 hr
2 days
7days
Time
Fig.2 Survivals with transplantated livers after perfusion preservation with PHP solution
with the grafts preserved for 24 hours with perfluorochemicalcontaining perfusates compared to 7 out of 8 dogs with the PIW solution. Of these, one of 5 dogs with the grafts perfused with the PHP solution containing high Na. high K and bicarbonate survived long. Furthermore, 4 of 10 dogs receiving the grafts n recovcrcd preserved for 48 hours with this particular compos consciousness and survived up to 2 days ( Fig. 2 ) . 3)Successful perfusion of rat small intestine : Small intestine transplantations have been done between Lewis rats. Intestinal grafts were preserved for different periods after irrigation of the vascular bed with Collins solution, University Wisconsin solution or the PHP solution at 4 degree centigrade. For the latest, contlnuous irrigation of the
iM
542
A G I S H I ET A L .
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
Smal I Intestine Transplant at ion survival 1 4 ws after Tx survival (24ws) out of 6+ 7-
6
Preservation period (brd
12 24
654-
32-
1-
Group I Fig.3
Col I ins Group II
uw
PHP
Group Ill
GrouplV
solution
Survivals with transplanted small intestine after preservation with Collins. UW or PHP solution
intestinal lumen with the PHP solution bubbled with oxygen gas was added. Five of 6 animals transplanted with the grafts preserved for 12 hours with the PHP solution survied f o r longer than 4 weeks while only 3 of 6 survived in other groups. There was no difference among the groups transplanted with the grafts preserved for 6 or 24 hours ( Fig. 3 ) . 4)Removal of antibodies : Exchange transfusion used to be clinically applied as a treatment modality f o r removal of ABO or Rh mismacch antibodles. Animal experiment showed availability, efficacy and safety of the PHP solution as a transfusate in new type of exchange transfusion. whole body rinse-out$ 1 . The PHP solution was tnvestigated for applicability as a transfusate to remove antibodies. Exchange transfusion was done in Lewis rats with 30 -
MODIFIED HEMOGLOBIN SOLUTION AS PERFUSATE
543
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
Exchange Transfusion with PHP Soluion -reduction in Igs-
25%
Time Fig.4
Reduction in immunoglobulins after exchange transfusion with PHP solution
60 ml of the PHP solution as transfusate. IgG decreased to 0 % to
an initial value immediately after exchange transfusion, IgA decreased to 24 t and IgM decreased to 21 %. and gradually recovered to a pretreatment level until 14th day. This technique is expected to be specially applied for removal of the naturally existing antibodies in xenotransplantation in order to prevent hyperacute rejection crisis which may occur immediately after transplantation with a very high incidence of irreversibllity ( Fig. 4 ) . REFERENCES 1)Matsushita Y. Iwashita Y. Iwasaki K et al. Physiologic effects of pyridoxylated-hemoglobin-polyethyleneglycol conjugate solution in exchange transfusion. Trans h e r SOC Artif Intern Organs 32:490-494.1986.
Downloaded by [University of California Santa Barbara] at 00:37 04 April 2016
544
AGISHI ET AL.
2)Agishi T, Funakoshi Y, Honda H et al.(Pyridoxylated hemoglobin)-(polyoxyethylene) conjugate solution as blood substitute for normothermic whole body rinse-out. Biomaterials, Artificial Cells and Artificial Organs 16(1-3):261-270.1988. 3)Sonda K. Agishi T. Suzukl T et al. Amelioration of renal ischemic damage by perfusion with stabilized hemoglobin solution. Jpn J Artif Organs 18(1):361-364.1889. 4)Fuchinoue S . Agishi T, Nakajima I. et al. Evaluation of (pyridoxylated hemoglobin)-(polyoxyethylene) conjugate solutlon as perfusate for liver preservation. A S A I O Transactions 33(3):390-394.1987. 5)Nakajima I. Fuchinoue S . Agishi T. et al. Twenty-four-hour liver preservation using artificial blood substitutes. Transplantation Proceedings 2O(Suppl 1):942-944.1988.
