Following myocardial infarction (MI), the resulting fibrotic scar is nonconductive and leads to ventricular dysfunction via electrical uncoupling of the remaining viable cardiomyocytes. The uneven conductive properties between normal myocardium and scar tissue result in arrhythmia, yielding sudden cardiac death/heart failure. A conductive biopolymer, poly-3-amino-4-methoxybenzoic acid-gelatin (PAMB-G), is able to resynchronize myocardial contractions in vivo. Intravenous PAMB-G injections into mice show that it does not cause any acute toxicity, up to the maximum tolerated dose (1.6 mL kg-1 ), which includes the determined therapeutic dose (0.4 mL kg-1 ). There is also no short- or long-term toxicity when PAMB-G is injected into the myocardium of MI rats, with no significant changes in body weight, organ-brain ratio, hematologic, and histological parameters for up to 12 months post-injection. At the therapeutic dose, PAMB-G restores electrical conduction in infarcted rat hearts, resulting in lowered arrhythmia susceptibility and improved cardiac function. PAMB-G is also durable, as mass spectrometry detected the biopolymer for up to 12 months post-injection. PAMB-G did not impact reproductive organ function or offspring characteristics when given intravenously into healthy adult rats. Thus, PAMB-G is a nontoxic, durable, and conductive biomaterial that is able to improve cardiac function for up to 1 year post-implantation.
Keywords: arrhythmia; cardiac function; conductive biopolymers; durability; poly-3-amino-4-methoxybenzoic acid-gelatin.
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