Fig. 4.

Sickle mice exhibit biventricular hypertrophy and microscopic multifocal ischemic changes and fibrosis. (A) Representative H&E-stained four-chamber views of WT, IDA, and sickle (Berk-SS) mouse hearts. Compared with an age- and gender-matched WT control, the 8-mo-old IDA mouse heart exhibits ventricular dilation but not hypertrophy after 3 mo of anemia. Biventricular hypertrophy and LA dilation are noted as early as 3 mo of age in the Berk-SS mouse. These findings worsen with age as evident in the 7-mo-old Berk-SS mouse. (B) H&E-stained mouse myocardium. Compared with an age- and gender-matched WT control (a), an 8-mo-old male Berk-SS mouse shows early ischemic changes characterized by loss of cross striations and decreased cardiomyocyte cytoplasmic eosinophilia (black arrows) (b). Late and more-severe ischemic changes, such as vanishing dead cardiomyocytes, are also noted in the Berk-SS mouse (d and e), and an occluded/congested microvessel with sickled RBC is noted adjacent to these ischemic changes (f, Inset). Microvessels are patent in the WT mouse (c, Inset).