The use of technetium tc 99m annexin V for in vivo imaging of apoptosis during cardiac allograft rejection Patrick W. Vriens, MDa, Francis G. Blankenberg,

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Presentation transcript:

The use of technetium tc 99m annexin V for in vivo imaging of apoptosis during cardiac allograft rejection Patrick W. Vriens, MDa, Francis G. Blankenberg, MDb, Jan H. Stoota, Katsuichi Ohtsuki, MDb, Gerald J. Berry, MDc, Jonathan F. Tait, MDd, H.William Strauss, MDb, Robert C. Robbins, MDa The Journal of Thoracic and Cardiovascular Surgery Volume 116, Issue 5, Pages 844-853 (November 1998) DOI: 10.1016/S0022-5223(98)00446-2 Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 1 Histologic grading of acute rejection in rats. Top left: Grade 0, no rejection (hematoxylin and eosin stain; original magnification ×400). Top right: Grade 1, mild rejection—sparse, focal or diffuse mononuclear cell infiltrate with no myocyte damage (hematoxylin and eosin stain; original magnification ×400). Bottom left: Grade 2, moderate rejection—focal or multifocal mononuclear cell infiltrate and myocyte damage (hematoxylin and eosin stain; original magnification ×400). Bottom right: Grade 3, severe rejection—diffuse mononuclear cell infiltrate and conspicuous myocyte damage (hematoxylin and eosin stain; original magnification ×200). The Journal of Thoracic and Cardiovascular Surgery 1998 116, 844-853DOI: (10.1016/S0022-5223(98)00446-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 2 Correlation between time after transplantation and histologic grade of acute rejection of heterotopic PVG allografts in untreated ACI rats. Histologic grades are as shown in Fig 1. Rejection was complete after 7.5 ± 0.5 days, as indicated by absence of palpable ventricular contractions. The Journal of Thoracic and Cardiovascular Surgery 1998 116, 844-853DOI: (10.1016/S0022-5223(98)00446-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 3 TUNEL staining in representative cardiac grafts. Top left: Absence of apoptosis in a graft that did not show histologic signs of acute rejection (original magnification, ×400). Top right: Absence of apoptosis in a graft after recovery from rejection, after 14 days of treatment with cyclosporine (original magnification ×400). Bottom left: Apoptotic nuclei of inflammatory cells in a graft with grade 2 rejection (original magnification ×400). Bottom right: Apoptotic nuclei of myocytes in a graft with grade 3 rejection (original magnification ×400). The Journal of Thoracic and Cardiovascular Surgery 1998 116, 844-853DOI: (10.1016/S0022-5223(98)00446-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 4 Uptake of 99mTc-annexin V on day 4 after transplantation in untreated ACI recipients in an allogeneic graft (arrow, A, group I) and a syngeneic graft (B, group II). Panels show representative images on day 4 after transplantation. The Journal of Thoracic and Cardiovascular Surgery 1998 116, 844-853DOI: (10.1016/S0022-5223(98)00446-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 5 Uptake of 99mTc-annexin V, measured as a percentage of total body uptake, in rejecting allogeneic PVG grafts (group I, filled bars), and nonrejecting syngeneic ACI grafts (group II, open bars), on days 1 through 7 after transplantation in untreated ACI recipients. Uptakes in grafts from groups I and II were compared on each day by a 2-tailed unpaired Student t test with unequal variance. The Journal of Thoracic and Cardiovascular Surgery 1998 116, 844-853DOI: (10.1016/S0022-5223(98)00446-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 6 Correlation between histologic grade of acute rejection and uptake of 99mTc-annexin V, measured as percentage of total body uptake. Histologic grades are as shown in Fig 1. Each data point represents an individual cardiac graft. The Journal of Thoracic and Cardiovascular Surgery 1998 116, 844-853DOI: (10.1016/S0022-5223(98)00446-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 7 Uptake of 99mTc-annexin V in an allogeneic graft from group III. ACI recipients received cyclosporine treatment (10 mg/kg/d) starting on day 4 after transplantation. A, Day 1 after transplantation, no treatment. B, Day 4 after transplantation, start of cyclosporine treatment. C, Day 11 after transplantation, after 7 days of cyclosporine treatment. D, Day 18 after transplantation, after 14 days of cyclosporine treatment, recovery from rejection. Panels show representative sequential images from 1 animal. The Journal of Thoracic and Cardiovascular Surgery 1998 116, 844-853DOI: (10.1016/S0022-5223(98)00446-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 8 Uptake of 99mTc-annexin V in PVG allografts of group III, as a percentage of total body uptake. ACI recipients received cyclosporine treatment starting on day 4 after transplantation. Uptakes in allografts from group III were compared on days 1, 4, 11, and 18 after transplantation by a 2-tailed paired Student t test with unequal variance. The Journal of Thoracic and Cardiovascular Surgery 1998 116, 844-853DOI: (10.1016/S0022-5223(98)00446-2) Copyright © 1998 Mosby, Inc. Terms and Conditions