(A) Under basal conditions, the ventricular dynamics of older (group 2) and younger (group 1) dogs differed in that group 2 exhibited significantly increased EDP and reduced EDV, consistent with increased stiffness. The expansion of intravascular volume by dextran accentuated this difference such that EDV increased in young dogs (group 1) while maintaining EDP below that of older dogs (group 2), which exhibited a smaller increase in volume but a larger increase in EDP. After 4 weeks of treatment with 1 mg/kg ALT-711 orally (group 2*), the EDV–EDP relationship in both basal and volume-expanded states moved toward that of the young animals, consistent with an increase in distensibility. (§ indicates a significant difference when compared with the older animals, whereas † indicates a significant difference between the pre- and posttreatment periods.) (B) Ventricular dynamics at baseline (group 3) and after 4 weeks of sham treatment (group 3‡) of a group of older dogs with identical characteristics to the treated group (group 2). The EDP–EDV relationship remained unchanged at baseline and after volume expansion.

Stroke volume index at baseline (group 2) significantly improves after treatment with ALT-711 (group 2*). §, P < 0.05 versus pretreatment basal value.