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. 2017 May 4;2(9):e93577. doi: 10.1172/jci.insight.93577

Figure 3. Transfusion-related mortality in guinea pigs with preexisting vascular remodeling and endothelial dysfunction is reversed by apo-transferrin (apo-Tf) and haptoglobin (Hp).

Figure 3

(A) Nine units S-RBCs significantly increased 7-day mortality in high-fat and high-sucrose diet (HFSD) but not in normal diet (ND) guinea pigs over a 7-day observation period (n = 10, P = 0.0143, by log-rank [Mantel-Cox]); data are presented as percentage survival. (B) Survival after a 7-day observation period of ND and HFSD guinea pigs after different transfusion regimens with increasing RBC transfusion dose as indicated. Administration of apo-Tf (300 mg/kg) and Hp (300 mg/kg) at the time of transfusion restores survival in the HFSD animals dosed with 9 units of S-RBCs at the highest RBC transfusion dose (apo-Tf; n = 10, *P = 0.0001, ANOVA with a multiple comparisons test) and (Hp; n = 10, †P = 0.0001, ANOVA with a multiple comparisons test). (C) Left panel: H&E staining of thoracic aorta showing large thrombi in a nonsurviving 9-unit S-RBC–transfused animal. Original magnification, ×400. Scale bar: 200 μm. Right panel: High magnification of dashed box region. Original magnification, ×200. Scale bar: 50 μm. (D) Left panel: Verhoeff-Van Geison staining of elastic fibers from the same animal in C. Original magnification, ×400. Scale bar: 200 μm. Right panel: High magnification of dashed box region showing extensive elastin fragmentation indicated by white arrows. Original magnification, ×100. Scale bar: 50 μm. (E) Left panel: Masson’s trichrome staining of collagen from the same animal in C. Original magnification, ×400. Scale bar: 200 μm. Right panel: High magnification of dashed box region showing collagen deposition indicated by solid arrows. Original magnification, ×100. Scale bar: 50 μm. (F) Left panel: H&E staining of renal cortical tissue from a separate nonsurviving animal showing acute proximal and distal tubule necrosis (solid arrow). Original magnification, ×200. Scale bar: 50 μm. Right panel: High magnification of dashed box region showing loss of renal cortical tubule nuclei (solid arrows) and thrombi occurring in the glomerular capillary structure (white arrow). Original magnification, ×600. Scale bar: 20 μm. All images were captured identically with default settings. Magnification = ocular lens (×10) × objective.