Evaluation Of Vasomera (Tm), A Novel Vpac2-Selective Vasoactive Intestinal Peptide Agonist, In Rats With Doxorubicin-Induced Cardiomyopathy: Evidence For Chronic Cardio-Protection

The natural vasoactive intestinal peptide (VIP) has been proposed as a therapeutic agent for heart failure via the activation of the G-protein-coupled VPAC1 and VPAC2 receptors; however, VIP9s clinical utility is limited due to its short half-life and VPAC1-mediated side-effects. Vasomera™ is a novel long-acting biopolymer-based selective VPAC2-receptor agonist. Here, the chronic functional/geometrical effects of Vasomera when given daily to rats with doxorubicin-induced cardiomyopathy were evaluated. Sprague-Dawley rats were assigned to receive daily therapy with either Vasomera (9 mg/kg/day SQ; n = 15) or placebo (n = 10), and had heart failure induced via doxorubicin (DOXO, 3 mg/kg IP on M-W-F for 2 weeks; 18 mg/kg total); treatments started prior to HF induction (5 days) and continued until the end of the study. LV function/geometry were evaluated (via echo) prior to the start of dosing, as well as weekly during/after (for up to 3 weeks) HF induction. Animals were terminally studied to evaluate LV mechano-energetics. DOXO lead to marked LV dysfunction/remodeling, characterized by depressed systolic function (e.g., FS: -18 ± 4 %, P